The Islet Isolation and Transplantation Core will provide Project investigators with a reliable supply of isolated mouse, rat, and human pancreatic islets for use in transplantation. Mouse and rat islets will be prepared by the personnel of the Core. Human islets will be obtained from Dr. Camillo Ricordi at the University of Miami. The Islet Core will supervise the receipt, assessment, counting, and distribution of the human islets. Core personnel will also perform all islet transplantation surgery. The need for this Core was recognized in our previous proposal, and our laboratory has supported the activities of an Islet Isolation Core since 1991. The need for the core is determined by both biological and logistical considerations. Islets comprise less than 1% of the mass of the pancreas, are distributed nearly uniformly throughout a gland laden with digestive enzymes, and are fixed in position by a network of vasculature and fibrous tissue. Their isolation is a time-consuming procedure that requires considerable skill. On average, each mouse or rat islet transplant recipient requires all the islets that can be obtained from about four donors. In our experience, one technician can process enough donors to transplant 3 to 4 chemically diabetic mice per day. Each mouse requires 20 islets per gram of body weight to restore normoglycemia. Program Project investigators anticipate performing 1,500 to 2,000 transplants yearly, all using mouse recipients. One technician engaged in islet isolation will be required to satisfy the projected need for mouse and rat tissue and to transplant all mouse, rat, and human islets. The procedures required for islet transplantation beneath the kidney capsule require the development and maintenance of surgical skill. The level of skill required is particularly high because of the need to maintain strict asepsis; many of the transplants will be performed using immunodeficient scid mice. The proposed Islet Isolation Core facility is intended to avoid duplication of effort in the Program Project's laboratories and enhance quality control. The Core will also facilitate the Program Project concept by standardizing a key shared methodology, allowing comparisons of results among Projects. Our islet isolation procedure is a modified collagenase method carried out under aseptic conditions. If investigators should require additional processing of islets in the form of prolonged culture to remove passenger leukocytes or the preparation of porcine islets, the Islet Core can also provide this service. Islet transplantation will be performed by the Core staff in viral antibody free quarters in the case of rat recipients and in a special quarantine facility in the case of scid mice.